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• Journal article
  Austin DJ, Anderson RM, 1996,

  Immunodominance, competition and evolution in immunological responses to helminth parasite antigens

  , Parasitology, Vol: 113, Pages: 157-172, ISSN: 0031-1820

  The paper describes the development and analysis of a mathematical framework for the study of the within-host population dynamics of the interaction between macroparasites and the human immune system. Simple models of this interaction based on the proliferation of T cell clones specific to parasite antigen, and the impact of clonal expansion on parasite survival, capture the basic features of age-related changes in worm loads within human communities. The model is generalized to multiple epitopes on a single antigen, and reveals competitive exclusion amongst T cells, with a single clone becoming immunodominant in the absence of cross-reactive responses and genetic variation. The introduction of genetic heterogeneity and concomitant variability in the immunogenicity of specific epitopes induces additional complexity into the dynamical interaction. Most importantly, multiple epitope models with antigenic variation suggest that the immunodominant response may not necessarily be targeted at the epitope at which some strains show the greatest immunogenicity. High immunogenicity at a particular epitope can be masked by genetic variability even though many of the variants are more immunogenic at this epitope by comparison with the epitope to which the immunodominant immunological response is directed.

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  • Citations: 12
• Journal article
  Ferguson NM, Anderson RM, Garnett GP, 1996,

  Mass vaccination to control chickenpox: the influence of zoster

  , Proc Natl Acad Sci U S A, Vol: 93, Pages: 7231-7235, ISSN: 0027-8424

  The impact of transmission events from patients with shingles (zoster) on the epidemiology of varicella is examined before and after the introduction of mass immunization by using a stochastic mathematical model of transmission dynamics. Reactivation of the virus is shown to damp stochastic fluctuations and move the dynamics toward simple annual oscillations. The force of infection due to zoster cases is estimated by comparison of simulated and observed incidence time series. The presence of infectious zoster cases reduces the tendency for mass immunization to increase varicella incidence at older ages when disease severity is typically greater.

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• Journal article
  Anderson RM, Donnelly CA, Ferguson NM, Woolhouse ME, Watt CJ, Udy HJ, MaWhinney S, Dunstan SP, Southwood TR, Wilesmith JW, Ryan JB, Hoinville LJ, Hillerton JE, Austin AR, Wells GAet al., 1996,

  Transmission dynamics and epidemiology of BSE in British cattle

  , Nature, Vol: 382, Pages: 779-788, ISSN: 0028-0836

  A comprehensive analysis of the bovine spongiform encephalopathy (BSE) epidemic in cattle in Great Britain assesses past, present and future patterns in the incidence of infection and disease, and allows a critical appraisal of different culling policies for eradication of the disease.

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• Journal article
  Garnett GP, Ferguson NM, 1996,

  Predicting the effect of varicella vaccine on subsequent cases of zoster and varicella

  , Rev Med Virol, Vol: 6, Pages: 151-161, ISSN: 1052-9276
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• Journal article
  Ferguson NM, Nokes DJ, Anderson RM, 1996,

  Dynamical complexity in age-structured models of the transmission of the measles virus: epidemiological implications at high levels of vaccine uptake

  , Math Biosci, Vol: 138, Pages: 101-130, ISSN: 0025-5564

  This article explores the effect of increasingly finely stratified age structure on the dynamical properties of deterministic metapopulation models of the transmission of the measles virus. The dynamical simplicity of earlier age-structured models is shown to break down once the age-specific force of infection is no longer assumed to be constant across all child age classes below 5 years of age. While the biennial epidemics characteristic of earlier models are still observed, additional higher period stable cycles arise and coexist with the biennial cycle. The existence of multiple stable limit cycles necessarily implies model sensitivity on initial conditions, and for certain parameter values, chaotic dynamics are observed. Using a novel parameterization of the magnitude of seasonal forcing we are also able to make more biologically relevant comparisons between the dynamics of age- and non-age-structured models than have hitherto been possible. The epidemiological significance of these results is discussed, and we demonstrate that perturbations of the kind produced by intensive vaccination programs can shift transmission dynamics between biennial and triennial cycles. The possible implications of this work for studies of intermittency and infection persistence are also considered.

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• Journal article
  DONNELLY CA, 1995,

  THE SPATIAL-ANALYSIS OF COVARIATES IN A STUDY OF ENVIRONMENTAL EPIDEMIOLOGY

  , STATISTICS IN MEDICINE, Vol: 14, Pages: 2393-2409, ISSN: 0277-6715
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  • Citations: 1
• Journal article
  ANDERSON RM, MAY RM, GUPTA S, 1995,

  GENETIC-HETEROGENEITY IN HELMINTHS - A REPLY

  , PARASITOLOGY, Vol: 111, Pages: 537-538, ISSN: 0031-1820
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  • Citations: 3
• Journal article
  Gregson S, Zhuwau T, Anderson RM, Chimbadzwa T, Chiwandiwa SKet al., 1995,

  Age and religion selection biases in HIV-1 prevalence data from antenatal clinics in Manicaland, Zimbabwe.

  , Cent Afr J Med, Vol: 41, Pages: 339-346, ISSN: 0008-9176

  Sera from 487 women attending antenatal clinics in two areas of Manicaland were tested for the presence of HIV-1 infection. In the Honde Valley and Rusitu Valley areas, 24,3 pc and 14 pc respectively, were found to be infected. HIV-1 infection was found to be associated with age, marital status and location. Younger women, non-married women and women living in the Honde Valley were all more likely to be infected. There was also a weak association with level of education, with women with secondary education being at greater risk of being infected. The unadjusted overall figures for HIV-1 prevalence from the antenatal clinics were shown to provide a poor indication of the relative levels of prevalence of infection in the two study areas because of differences in the age structure and religious affiliations of the antenatal clinic and study populations. Similar problems may exist in sentinel surveillance data and would distort comparisons between locations and over time, especially during periods of rapid fertility change. In particular, the age bias is liable to exaggerate differences between urban and rural populations in developing societies. Where comparable information is available for the general population and sample sizes permit, this problem may be overcome by collecting basic socio-demographic data on the individuals tested and then applying standardization techniques. In the Honde Valley and Rusitu Valley example, the levels of HIV-1 prevalence after adjusting for age differences are 18,4 pc and 13,2 pc respectively.

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• Journal article
  DONNELLY CA, SETH J, CLAYTON RM, PHILLIPS CI, CUTHBERT J, PRESCOTT RJet al., 1995,

  SOME BLOOD-PLASMA CONSTITUENTS CORRELATE WITH HUMAN CATARACT

  , BRITISH JOURNAL OF OPHTHALMOLOGY, Vol: 79, Pages: 1036-1041, ISSN: 0007-1161
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  • Citations: 27
• Journal article
  DONNELLY CA, LAIRD NM, WARE JH, 1995,

  PREDICTION AND CREATION OF SMOOTH CURVES FOR TEMPORALLY CORRELATED LONGITUDINAL DATA

  , JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, Vol: 90, Pages: 984-989, ISSN: 0162-1459
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  • Citations: 17

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